Biological injection therapy with leukocyte-poor platelet-rich plasma induces cellular alterations, enhancement of lubricin, and inflammatory downregulation in vivo in human knees: A controlled, prospective human clinical trial based on mass spectrometry imaging analysis

Axel W Baltzer; Rita Casadonte; Alexei Korff; Lea Merline Baltzer; Katharina Kriegsmann; Mark Kriegsmann; Jörg Kriegsmann

doi:10.3389/fsurg.2023.1169112

Biological injection therapy with leukocyte-poor platelet-rich plasma induces cellular alterations, enhancement of lubricin, and inflammatory downregulation in vivo in human knees: A controlled, prospective human clinical trial based on mass spectrometry imaging analysis

Front Surg. 2023 Apr 21:10:1169112. doi: 10.3389/fsurg.2023.1169112. eCollection 2023.

Authors

Axel W Baltzer¹, Rita Casadonte², Alexei Korff¹, Lea Merline Baltzer³, Katharina Kriegsmann⁴, Mark Kriegsmann^{5

6}, Jörg Kriegsmann^{2

7

8}

Affiliations

¹ Center for Molecular Orthopaedics, MVZ Ortho Koenigsallee, Düsseldorf, Germany.
² Imaging Mass Spectrometry, Proteopath GmbH, Trier, Germany.
³ Klinik für Zahnmedizin, Uniklinik RWTH, Aachen, Germany.
⁴ Department for Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.
⁵ Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
⁶ Germany Translational Lung Research Centre Heidelberg, Member of the German Centre for Lung Research (DZL), Heidelberg, Germany.
⁷ MVZ-Zentrum für Histologie, Zytologie und Molekulare Diagnostik, Trier, Germany.
⁸ Department of Medicine, Faculty of Medicine/Dentistry, Danube Private University, Krems, Austria.

Abstract

Objective: To investigate the in vivo biological effects of leukocyte-poor platelet-rich plasma (LpPRP) treatment in human synovial layer to establish the cellular basis for a prolonged clinical improvement.

Methods: Synovial tissues (n = 367) were prospectively collected from patients undergoing arthroscopic surgery. Autologous-conditioned plasma, LpPRP, was injected into the knees of 163 patients 1-7 days before surgery to reduce operative trauma and inflammation, and to induce the onset of regeneration. A total of 204 patients did not receive any injection. All samples were analyzed by mass spectrometry imaging. Data analysis was evaluated by clustering, classification, and investigation of predictive peptides. Peptide identification was done by tandem mass spectrometry and database matching.

Results: Data analysis revealed two major clusters belonging to LpPRP-treated (LpPRP-1) and untreated (LpPRP-0) patients. Classification analysis showed a discrimination accuracy of 82%-90%. We identified discriminating peptides for CD45 and CD29 receptors (receptor-type tyrosine-protein phosphatase C and integrin beta 1), indicating an enhancement of musculoskeletal stem cells, as well as an enhancement of lubricin, collagen alpha-1-(I) chain, and interleukin-receptor-17-E, dampening the inflammatory reaction in the LpPRP-1 group following LpPRP injection.

Conclusions: We could demonstrate for the first time that injection therapy using "autologic-conditioned biologics" may lead to cellular changes in the synovial membrane that might explain the reported prolonged beneficial clinical effects. Here, we show in vivo cellular changes, possibly based on muscular skeletal stem cell alterations, in the synovial layer. The gliding capacities of joints might be improved by enhancing of lubricin, anti-inflammation by activation of interleukin-17 receptor E, and reduction of the inflammatory process by blocking interleukin-17.

Keywords: LpPRP; MALDI-mass spectrometry; disease-modifying therapy; inflammation; lubricin; osteoarthritis; platelet-rich plasma.